Table 3.
Antineoplastic activity of avapritinib in a Phase I study (EXPLORER) of patients with AdvSM (median duration of treatment 14 months (Part 1) and 5 months (Part 2)
| Best response (n, %) | Part 1: Dose escalation Phase (30–400 mg daily); n=32 | Part 2: Dose expansion Phase (300 mg daily); n=20 | All patients; N=52 |
|---|---|---|---|
| Bone marrow MC burden | n=27 | n=9 | n=36 |
| <50% decrease in neoplastic MCs | 3 (11%) | 0 | 3 (8%) |
| ≥50% decrease in neoplastic MCs | 8 (30%) | 4 (44%) | 12 (33%) |
| No evidence of neoplastic MCs | 16 (59%) | 5 (56%) | 21 (58%) |
| Serum tryptase | n=32 | n=18 | n=50 |
| <50% decrease | 0 | 1 (6%) | 1 (2%) |
| ≥50% decrease | 8 (25%) | 8 (44%) | 16 (32%) |
| <20 μg/L | 24 (75%) | 9 (50%) | 33 (66%) |
| Splenomegaly | n=11 | n=8 | n=19 |
| <35% decrease in size by imaging or 50% decrease by palpation | 0 | 1 (13%) | 1 (5%) |
| ≥35% decrease in size by imaging or ≥50% decrease by palpation | 5 (45%) | 4 (50%) | 9 (47%) |
| Normal spleen size by imaging or palpation | 6 (55%) | 3 (38%) | 9 (47%) |
| BM KITD816V mutant allele burden | n=26 | n=16 | n=42 |
| Any increase | 0 | 1 (6%) | 1 (2%) |
| <50% decrease | 3 (12%) | 1 (6%) | 4 (10%) |
| ≥50% decrease | 23 (88%) | 14 (88%) | 37 (88%) |
| Patients with mastocytosis in skin | n=14 | n=9 | n=23 |
| Improvement based upon investigator evaluation | 13 (93%) | 7 (78%) | 20 (87%) |
Note: Copyright © 2018. Dove Medical Press. Reproduced from Deininger MW, Gotlib J, Robinson WA, et al. Avapritinib (BLU-285), a selective KIT inhibitor, is associated with high response rate and tolerable safety profile in advanced systemic mastocytosis (AdvSM): results of a phase 1 study. EHA Annual Meeting, 2018. Abstract PF612.87
Abbreviation: MCs, mast cells.